Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials
Trial record 1 of 1 for:    NCT01820364
Previous Study | Return to List | Next Study

LGX818 in Combination With Agents (MEK162; BKM120; LEE011; BGJ398; INC280) in Advanced BRAF Melanoma (LOGIC)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01820364
First received: March 25, 2013
Last updated: July 29, 2014
Last verified: July 2014

March 25, 2013
July 29, 2014
November 2013
August 2016   (final data collection date for primary outcome measure)
Overall response rate [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01820364 on ClinicalTrials.gov Archive Site
  • Incidence and severity of adverse events [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
  • Incidence rate of Dose Limiting Toxicities (DLTs) in Cycle 1 of Combination Part (Part II) [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
  • Plasma concentration and derived PK parameters of LGX818 and combination partners [ Time Frame: 3years ] [ Designated as safety issue: Yes ]
  • Overall Response Rate (ORR) (Part I) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Progression Free Survival (PFS)(Part I and II) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Duration Of Response (DOR) (Part II) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Overall Survival (OS) (Part II) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Molecular status (mutation/amplification/expression) of markers relevant to the RAF/MEK/ERK and PI3K/AKT pathways [ Time Frame: baseline, at progression with LGX818 single agent treatment up to 3 years ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
LGX818 in Combination With Agents (MEK162; BKM120; LEE011; BGJ398; INC280) in Advanced BRAF Melanoma
Phase II, Multi-center, Open-label Study of Single-agent LGX818 Followed by a Rational Combination With Agents After Progression on LGX818, in Adult Patients With Locally Advanced or Metastatic BRAF V600 Melanoma

The primary purpose of the Phase II CLGX818X2102 study is to assess the anti-tumor activity of LGX818 in combination with selected agents.

This is a phase II two part multi-center, open-label study. Part I: LGX818 single agent treatment until progression Part II: Combination treatments of LGX818 + MEK162, or BKM120, or BGJ398, or INC280, or LEE01 to assess the clinical efficacy, to further evaluate the safety of the drug combinations in patients with locally advanced or metastatic BRAF mutant melanoma after relapse on LGX818, and to determine the maximum tolerated dose of the combinations (when not established previously). These drug combinations are selected and assigned to patients based on documentation of molecular resistance mechanism.

Patients with BRAF mutant melanoma treated by LGX818 single agent in other studies can be enrolled directly in Part II of CLGX818X2102 after relapse.

Dose-escalations in the combination arms for which no MTD has been established will be based on the recommendations of a Bayesian logistic regression model guided by an escalation with overdose control criterion

Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Melanoma
  • Drug: LGX818
    BRAF inhibitor
  • Drug: MEK162
    MAPK1/2 inhibitor
  • Drug: LEE011
    CDK4/6 inhibitor
  • Drug: BGJ398
    FGFR inhibitor
  • Drug: BKM120
    Pi3K inhibitor
  • Drug: INC280
    c-Met inhibitor
  • Experimental: LGX818 + MEK162
    Rational combination of LGX818 + MEK162
    Interventions:
    • Drug: LGX818
    • Drug: MEK162
  • Experimental: LGX818 + LEE011
    Rational combination of LGX818 + LEE011
    Interventions:
    • Drug: LGX818
    • Drug: LEE011
  • Experimental: LGX818 + BGJ398
    Rational combination of LGX818 + BGJ398
    Interventions:
    • Drug: LGX818
    • Drug: BGJ398
  • Experimental: LGX818 + BKM120
    Rational combination of LGX818 + BKM120
    Interventions:
    • Drug: LGX818
    • Drug: BKM120
  • Experimental: LGX818 + INC280
    Rational combination of LGX818 + INC280
    Interventions:
    • Drug: LGX818
    • Drug: INC280
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
100
August 2016
August 2016   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • locally advanced or metastatic melanoma
  • confirmed BRAF V600 mutation
  • patients naïve to a selective BRAF inhibitor
  • fresh tumor biopsy at baseline, and patient agrees for a mandatory biopsy at the time of relapse
  • life expectancy ≥ 3 months
  • World Health Organization (WHO) Performance Status ≤ 2.

Exclusion Criteria:

  • Previous treatment with RAF-inhibitor
  • Symptomatic or untreated leptomeningeal disease
  • Symptomatic brain metastases.
  • Known acute or chronic pancreatitis
  • Clinically significant cardiac disease
  • AST/SGOT and ALT/SGPT > 2.5 x ULN, or > 5 x ULN if liver metastases are present
  • Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral interventional drug
  • Previous or concurrent malignancy.
  • Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation

Specific exclusion criteria for each treatment arm:

LGX818/MEK162:

History or current evidence of retinal disease History of Gilbert's syndrome.

LGX818/BKM120:

Patients with diabetes mellitus requiring insulin treatment Patient has mood disorders

LGX818/BGJ398:

History and/or current evidence of ectopic mineralization/ calcification Current evidence of corneal disorder/ keratopathy Patients with current evidence of endocrine alteration of calcium/phosphate homeostasis.

History of congenital long QT- syndrome and/or hypokalaemia CTCAE Grade ≥ 3 and/or magnesium levels below the clinically relevant lower limits before study entry.

Ionized (i) calcium (Ca) > ULN Serum inorganic phosphorus (Pi) > ULN

LGX818/LEE011 History of congenital long QT- syndrome and/or hypokalaemia CTCAE Grade ≥ 3 and/or magnesium levels below the clinically relevant lower limits before study entry.

Both
18 Years and older
No
Contact: Novartis Pharmaceuticals 1-888-669-6682
Contact: Novartis Pharmaceuticals
United States,   Australia,   Canada,   France,   Germany,   Netherlands,   Spain,   Switzerland
 
NCT01820364
CLGX818X2102, 2012-004798-17
Not Provided
Novartis ( Novartis Pharmaceuticals )
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP